Prognostic and therapeutic insights into colorectal carcinoma through immunogenic cell death gene profiling

Jinglu Yu1, Yabin Gong2, Zhenye Xu3

  • 1PuDong Traditional Chinese Medicine Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China, Shanghai, Pudong, China.

Peerj
|June 28, 2024
PubMed

Insights

This study introduces a new immunogenic cell death (ICD) score to predict colorectal cancer patient outcomes and immunotherapy response. Higher ICD scores indicate a better response to cancer treatments.

Area of Science:

  • Oncology
  • Immunology
  • Genomics

Background:

  • Immunogenic cell death (ICD) is crucial in oncology, but its role in colorectal carcinoma is not fully understood.
  • Understanding ICD's impact can improve treatment strategies for colorectal cancer.

Purpose of the Study:

  • To investigate the role of ICD in colorectal carcinoma.
  • To develop a novel ICD quantification system for predicting patient outcomes and immunotherapy effectiveness.
  • To identify molecular subtypes within colorectal cancer based on ICD characteristics.

Main Methods:

  • Utilized single-cell sequencing to create an ICD score within the tumor immune microenvironment (TIME).
  • Analyzed immunogenic cell death-related genes (ICDRGs) in 1,184 colorectal adenocarcinoma patients from TCGA and GEO datasets.
  • Employed Principal Component Analysis (PCA) for ICD score establishment and validated the model in three independent cohorts.

Main Results:

  • Identified two distinct molecular subtypes in colorectal adenocarcinoma based on ICD scores.
  • The developed ICD score accurately predicted immunotherapy success.
  • Patients with high ICD scores demonstrated a 'hot' immune phenotype and better immunotherapy response.
  • Key genes (AKAP12, CALB2, CYR61, MEIS2) were linked to increased tumor proliferation, invasion, and PD-L1 expression.

Conclusions:

  • The novel ICD score serves as a reliable predictor of patient prognosis and immunotherapy response in colorectal carcinoma.
  • Targeting ICD presents a promising strategy for advancing anti-tumor therapies in colorectal cancer.
  • The findings contribute to a deeper understanding of the tumor immune microenvironment in colorectal cancer.

Related Concept Videos